ACTONEL Film-coated tablet Ref.[50803] Active ingredients: Risedronic acid

Foods, drinks (other than plain water) and medicinal products containing polyvalent cations (such as calcium, magnesium, iron and aluminium) interfere with the absorption ofbisphosphonates and should not be taken at the same time as Actonel (see section 4.5). In order to achieve the intended efficacy, strict adherence to dosing recommendations is necessary (see section 4.2).

Efficacy ofbisphosphonates in the treatment of postmenopausal osteoporosis is related to the presence of low bone mineral density (BMD T-score at hip or lumbar spine S-2.5 SD) and/or prevalent fracture. High age or clinical risk factors for fracture alone are not reasons to initiate treatment of osteoporosis with a bisphosphonate.

The evidence to support efficacy ofbisphosphonates including Actonel in very elderly women (<80 years) is limited (see section 5.1).

Bisphosphonates have been associated with oesophagitis, gastritis, oesophageal ulcerations and gastroduodenal ulcerations. Thus caution should be used:

• In patients who have a history of oesophageal disorders which delay oesophageal transit or emptying e.g. stricture or achalasia.
• In patients who are unable to stay in the upright position for at least 30 minutes after taking the tablet.
• If risedronate is given to patients with active or recent oesophageal or upper gastrointestinal problems (including known Barrett’s oesophagus).

Prescribers should emphasise to patients the importance of paying attention to the dosing instructions and be alert to any signs or symptoms of possible oesophageal reaction. The patients should be instructed to seek timely medical attention if they develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing, retrosternal pain or new/worsened heartburn.

Hypocalcaemia should be treated before starting Actonel therapy. Other disturbances of bone and mineral metabolism (e.g. parathyroid dysfunction, hypovitaminosis D) should be treated at the time of starting Actonel therapy.

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphophonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates.

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors (e.g. cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene).

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation ofbisphosphonate treatment reduces the risk of osteonecrosis of the jaw. Clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with longterm therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.

Atypical fractures of the femur

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation ofbisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit/risk assessment.

During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

No formal interaction studies have been performed, however no clinically relevant interactions with other medicinal products were found during clinical studies.

Concomitant ingestion of medications containing polyvalent cations (e.g. calcium, magnesium, iron and aluminium) will interfere with the absorption ofrisedronate sodium (see section 4.4).

Risedronate sodium is not systemically metabolised, does not induce cytochrome P450 enzymes, and has low protein binding.

In the risedronate sodium Phase III osteoporosis studies, acetyl salicylic acid or NSAID use was reported by 33% and 45% of patients respectively.

If considered appropriate risedronate sodium may be used concomitantly with oestrogen supplementation.

There are no adequate data from the use of risedronate sodium in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Studies in animal indicate that a small amount of risedronate sodium pass into breast milk.

Risedronate sodium must not be used during pregnancy or by breast-feeding women.

Actonel has no or negligible influence on the ability to drive and use machines.

Risedronate sodium has been studied in phase III clinical studies involving more than 15,000 patients. The majority of undesirable effects observed in clinical studies was mild to moderate in severity and usually did not require cessation of therapy.

Adverse experiences reported in phase III clinical studies in postmenopausal women with osteoporosis treated for up to 36 months with risedronate 5 mg/day (n 5020) or placebo (n 5048) and considered possibly or probably related to risedronate are listed below using the following convention (incidences versus placebo are shown in brackets): very common (21110); common (211100; <1110); uncommon (2111,000; <11100); rare (21110,000; <111,000); very rare (<1110,000).

Nervous system disorders

Common: headache (1.8% vs. 1.4%)

Eye disorders

Uncommon: iritis*

Gastrointestinal disorders

Common: constipation (5.0% vs. 4.8%), dyspepsia (4.5% vs. 4.1%), nausea (4.3% vs. 4.0%), abdominal pain (3.5% vs. 3.3%), diarrhoea (3.0% vs. 2.7%)

Uncommon: gastritis (0.9% vs. 0.7%), oesophagitis (0.9% vs. 0.9%), dysphagia (0.4% vs. 0.2%), duodenitis (0.2% vs. 0.1%), oesophageal ulcer(0.2%vs. 0.2%)

Rare: glossitis (<0.1% vs. 0.1%), oesophageal stricture (<0.1% vs. 0.0%),

Musculoskeletal and connective tissues disorders

Common: musculoskeletal pain (2.1% vs. 1.9%)

Investigations

Rare: abnormal liver function tests*

^* No relevant incidences from Phase III osteoporosis studies; frequency based on adverse event/laboratory/rechallenge findings in earlier clinical studies.

Laboratory findings

Early, transient, asymptomatic and mild decreases in serum calcium and phosphate levels have been observed in some patients.

The following additional adverse reactions have been reported during post-marketing use (frequency unknown):

Eye disorders

Iritis, uveitis

Musculoskeletal and connective tissues disorders

Osteonecrosis of the jaw

Skin and subcutaneous tissue disorders

Hypersensitivity and skin reactions, including angioedema, generalised rash, urticaria and bullous skin reactions, some severe including isolated reports of Stevens-Johnson syndrome toxic epidermal necrolysis and leukocytoclastic vasculitis. hair loss.

Immune system disorders

Anaphylactic reaction

Hepatobiliary disorders

Serious hepatic disorders. In most of the reported cases the patients were also treated with other products known to cause hepatic disorders.

During post-marketing experience the following reactions have been reported:

Rare: Atypical subtrochanteric and diaphyseal fermoral fractures (bisphosphonate class adverse reaction). Very rare: Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6767836. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

Not applicable.